The homotrimeric structure of HtrA2 is indispensable for executing its serine protease activity

Min Kyung Nam, Young Mo Seong, Hyo Jin Park, Ju Youn Choi, Seongman Kang, Hyangshuk Rhim

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

Serine protease activity of high temperature requrement 2 (HtrA2) is essential for promoting cell death, as well as for protecting against cellular stresses. An X-ray crystallographic study described the formation of a pyramid shaped homotrimer that is a proteolytically competent form of HtrA2; however, little is known about effects of the trimeric structure of HtrA2 on the natural substrates. In this study, we generated the HtrA2 protein that has a single point mutation at the homotrimerization motif to assess relationship between structure and the proteolytic activity of HtrA2 on its substrates. Using gel filtration, a native gel electrophoresis system, and a co-precipitation assay, we confirm that phenylalanine 149 in HtrA2 is a crucial determinant for the formation of the HtrA2 homotrimeric structure. Moreover, we described that the HtrA2 monomeric form abolished not only autoproteolytic activity, but also the proteolytic activity against XIAP (X-linked inhibitor of apoptosis protein) known as the HtrA2 substrate. Taken together, the results indicate that the homotrimeric structure of HtrA2 is required for executing its serine protease activity.

Original languageEnglish
Pages (from-to)36-43
Number of pages8
JournalExperimental and Molecular Medicine
Volume38
Issue number1
DOIs
Publication statusPublished - 2006 Feb 28

Keywords

  • Omi serine protease
  • Protein structure, tertiary
  • Serine endopeptidases
  • Structure-activity relationships
  • X-linked inhibitor of apoptosis protein

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

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